The present invention relates to peripheral vasodilators each comprising a carbostyril derivative as an active ingredient, as well as to novel carbostyril derivatives having an excellent peripheral vasodilating activity.
There have been made a number of studies on various carbostyril derivatives and their pharmacological activities. For example, Japanese Patent Application Kokai (Laid-Open) No. 3182/1989 describe that the carbostyril derivatives represented by the following general formula: ##STR2## [wherein, R is a group of the formula: ##STR3## or a group of the formula: ##STR4## (R.sup.1' is a group of the formula: --NR.sup.4' R.sup.5' or the like; R.sup.2' is a hydrogen atom or a lower alkyl group; and R.sup.3' is a hydrogen atom, a lower alkyl group or the like)] have a myocardial contraction increasing activity, a coronary blood flow increasing activity, a hypotensive activity, a norepinephrin vasocontraction inhibitory effect and an anti-inflammatory effect and are useful as a cardiotonic for treating various heart diseases, an anti-hypertensive agent and an anti-inflammatory agent. It is not known, however, that such carbostyril derivatives have a peripheral vasodilating activity.
In addition to the above, various carbostyril derivatives, each of which having chemical structural formula similar to that of the carbostyril derivative represented by the below-mentioned general formula (1), have been known in some prior art references, for example Japanese Patent Kokai (Laid-open) No. Sho 57-171974 (1982) [Japanese Patent Publication No. Sho 64-9313 (1989)]; Japanese Patent Kokai (Laid-open) No. Sho 57-154129 (1982) [Japanese Patent Publication No. Sho 64-53248 (1989)]; Japanese Patent Kokai (Laid-open) No. Sho 59-29668 (1984) [Japanese Patent Publication No. Hei 2-22751 (1990)]; Japanese Patent Kokai (Laid-open) Nos. Sho 54-16478 (1979); Sho 55-85520 (1980); Sho 51-65770 (1976); Sho 51-68574 (1976); Sho 51-118771 (1976); Sho 52-282 (1977); Sho 52-283 (1977); Sho 51-118474 (1977); Sho 52-83380 (1977); Sho 63-35562 (1988) as well as U.S. Pat. Nos. 4,487,772; 4,454,130; 4,468,402; 4,886,809; 5,071,856 (EP-A-0255134); U.S. Pat. No. 4,845,100 (EP-A-0202760); U.S. Pat. Nos. 4,514,401; 4,455,422; 4,567,187; 4,460,593; 4,619,932 and 5,008,274 (EP-A-0240015).
The carbostyril derivatives disclosed in the above-mentioned prior art references indeed possess certain pharmacological activities, for example myocardial contraction increasing activity (positive inotropic activity), coronary blood flow increasing activity, hypotensive activity and antiinflammatory activity, etc. However, such known carbostyril derivatives do not possess any peripheral vasodilating activities at all.
Hence, development of novel carbostyril derivatives having a peripheral vasodilating activity has been desired.